Category Archive: Tissue Engineering

  1. Changing the future of medicine with 3D Bioprinting

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    The creation of artificial human tissues and organs may sound like a futuristic dream, but it is happening right now. Research institutes and hospitals around the globe have been working on bioprinting applications, which are providing new options for treatment and scientific study. Potentially, 3d bioprinting will be the next big thing in health care and personalised medicine.

    The idea of printing human organs, has its origins  in the invention of stereolithography in 1983. This special type of 3D printing relied on a laser to solidify a polymer material extruded from a nozzle. However, the material used in this process was not robust enough to create a long-lasting structure. By the early 1990s, the next generation of materials was introduced. Called nanocomposites, they were blends of plastics and powdered metals. These materials were more durable. They made possible the scientist to produce longer lasting end-products.

    It did not take long for medical researchers to notice the protentional of such materials and 3d printing technology in clinical application. In 1999, scientists at the Wake Forest Institute for Regenerative Medicine used a 3D printer to build a synthetic scaffold of a human bladder. They then coated the scaffold with cells taken from their patients and successfully grew working organs. This set the stage for true bioprinting. In 2002, scientists printed a miniature functional kidney capable of filtering blood and producing urine in an animal model. And in 2010,Organovo printed the first blood vessel. Today, 3d bioprinting companies like Cellink, Allevi , Regemat or SunP are focusing on printer and living inks development to provide future opportunities for complex organ printing.

    Within bioprinting, there are three main technologies, namely inkjet, extrusion, and laser-assisted printing. Inkjet printers possess a print-head that generates a pressure pulse (either thermally or acoustically) that forces droplets from the nozzle. Laser-assisted printers use pressure generated by a laser to propel cell-containing material from an absorbing substrate onto a collect substrate. Finally, and most commonly used, are extrusion printers that use pneumatic or mechanical piston/screw dispensing systems to extrude continuous beads of bio-ink.

    There are also different biomaterials which are reported as bioinks for 3D bioprinting. They are the Agarose-based, Alginate-based, Collagen-based, Hyaluonic acid-based, Fibrin-based, Cellulose-based, Silk-based and Synthetic biomaterials. Each class of bioink has pros and cons, however, they have a common requirement for control of mechanical and biological properties of the printable material.In terms of mechanical control, it is imperative that the bioink forms a microstructure which mimics that of the cell’s native environment. As well as a familiar architecture, the gel stiffness and porosity should be matched to that found in vivo so as to support cell growth, signalling, and proliferation. Ideally, the bioink will exhibit shear-thinning behaviour, as this will reduce the stress exerted on the cells during the printing process, which most commonly involves extrusion of the bioink through a narrow print-head. In order to assure biocompatibility, the raw materials used for the production of the bioink should not be cytotoxic to the cells in question, nor elicit an immune or inflammatory response.

    Using a combination of the right printing process and bioink, researchers have already been printing bone and skin tissues in the labs. Whilst work towards the bioprinting of more complex internal organs, such as the liver, is happening today in research labs all across the world,  it is anticipated that  fully functioning lab grown versions of these are still at least 10 years away, possibly more.

     

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  2. Application of Biogelx synthetic hydrogels for osteogenic stimulation | Interview with Álvaro Sánchez Rubio

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    Álvaro Sánchez Rubio is one of our new Biogelx sponsored PhD students! His MRS funded project aims to apply novel synthetic hydrogels for osteogenic stimulation and to demonstrate their value for tissue engineering and bone repair. In this interview, he speaks about his research and shares his hands-on experiences working with our new BiogelxTM-Ink.

    1. Please tell us a little bit about yourself.

    My name is Álvaro. I was born and raised in Valencia, Spain which is still very close to my heart. Later I moved to Barcelona to study Biomedical Engineering. The opportunity to be educated in different cities allowed me to be involved with hospitals and laboratories in numerous geographical locations. I have found particularly interesting how technology and biology can intersect and provide opportunities for future developments in the healthcare field.

    I have a research interest in 3d bioprinting. I have been using 3D printing technology for 5-years. Currently, I am conducting Ph.D. research which focuses on the application of 3d bioprinting in bone regeneration.

    1. What research does you/your lab focus on? 

    Our lab is a highly interdisciplinary lab that focuses on understanding the interaction between materials, proteins, and cells to engineer and control cell behaviour and stem cell differentiation. Recently the institute’s bone tissue regeneration project has been shortlisted in the “Research Project of the Year: STEM” awarded by Research Impact and Times Higher Education.

    My research aims to investigate a system that can be used to obtain 3D printed cell-laden microarchitectures that mimic complex structures found in native bone. It includes investigating the effects of different materials, cell types and printing approaches.

    1. Why is it so important to use synthetic 3D hydrogels in your research? 

    Using synthetic hydrogels allows me to mitigate the risk of cross-contamination in my research, which is a possibility with animal-derived material. It is also an advantage of these materials that their physicochemical properties can be tuned, and their production is scalable.

    Speaking specifically about BiogelxTM peptide hydrogels, I would highlight their tunable stiffness by just changing the concentration. This key differentiator of these products is of paramount importance to me because the different stiffness matrices can control stem cells fate. Another important feature of BiogelxTM gels is that they are printable.

    One of the main benefits of 3D bioprinting technology is that the scientists can print computer-generated predesigned architectures allowing us to tailor specific scaffolds to patients or applications. Today, we have many different materials used in 3D bioprinting. However often they only provide a structural support which needs further processing to include the cells. By utilizing novel bio-ink materials like BiogelxTM, we can print cell-laden scaffolds that include homogeneous cell distribution within the printed architecture. This technology also allows us to create multi-material structures included the distribution of different cell types and different bio-inks.

    1. Have you tried any alternative bio-inks? What are the key features of a good bio-ink? 

    Yes, as I mentioned I have been working with 3d bioprinting technology for 5-years. Therefore, I have experience working with different bio-ink products available on the market. For my early work in 3D bioprinting, I used alginate bio-inks. I could print simple architectures, and the cellular behaviour was also sufficient. However, I found it to be insufficient to create complex microarchitectures.

    My opinion is that a good bio-ink have to provide a balance between biocompatibility, printer compatibility, convenient crosslinking method, appropriate degradation dynamics, and non-toxicity. Cost and availability also need to be considered. Nevertheless, different cell type may prefer different bio-inks, therefore the features of a good bio-ink may vary amongst different cell types.

    1. How easy is to use BiogelxTM-Ink?

    It is very easy to use BiogelxTM products. It might be one of the main advantages of BiogelxTM peptide hydrogels. The product preparation protocol is easy to follow. The hydrated pre-gel solution is obtained by adding water to the lyophilized powder. The BiogelxTM-Ink formulations are also very similar. When you print with Inks, you notice good shear-thinning behaviour. The viscosity of these materials allows you to see a nice 3D printed thread that does not have excessive lateral diffusion. The format the products are supplied in is also helpful. It ensures a higher control over the stock and contamination issues which can occur by using big pots or leaving them open for longer times.

    1. What cell types do you use in your research? Please share your experience in growing cells in our gel(s)/bioink.

    I am currently working with C2C12, an immortalized mouse myoblast line. They have been extensively used for research in muscle regeneration and are less expensive cells when compared with stem cells. However, I also plant to move onto to working with stem cells as well as some other cell types during my PhD project.

    When adding cells in 3D cultures using BiogelxTM products, you can obtain a homogeneous distribution of cells, which is crucial as having different cell densities will affect the result and make the process unreproducible.

    1. What are the next steps in your research?

    I just started my research; thus, I have a long way ahead. My aim in the first year is to develop a 3D bioprinting protocol that can be used, repeated and reproduced with robustness. I am also focusing on the exploration of how different cell types can be combined with the printing processes. I will use C2C12 or other fibroblast line and start some work along with Mesenchymal Stem Cells and HUVEC cells.

     

    The new BiogelxTM-Ink will be commercially available from next year. Watch this space for more info and details on the launch!

     

     

     

    You might like:

    What are the properties of an ideal bioink?

    Give me the best bioink! | A short guide to the currently available 3D bioinks

    When is a bioink not a bioink?